P0981Combination therapy with an immunomodulator improves persistence of anti-tumour necrosis factor agents but not vedolizumab or ustekinumab in Inflammatory Bowel Disease, with improved persistence seen with longer duration of initial combination therapy before de-escalation

Abstract Background Combination with an advanced therapy (AT) and immunomodulator (IMM) is commonly used to optimise Crohn’s disease (CD) and ulcerative colitis (UC). We aimed to assess the impact of IMM co-therapy on AT persistence. Methods We interrogated the Persistence Australian National IBD Cohort (PANIC5) registry from 2007-2021, covering all Australian prescribing data for CD and UC. We defined non-persistence as 6 months without dispensing, and IMM co-therapy as thiopurine or methotrexate use at any point during AT. Persistence was compared using log-rank tests and Cox proportional hazards. Results 19,087 CD and 9,671 UC patients underwent 31,967 and 14,784 lines of AT respectively, totaling 103,025 patient-years follow up. The proportions of CD and UC patients on IMM co-therapy with TNFi were 51.7% and 43.1% respectively; vedolizumab: 27.6% and 28.4%, ustekinumab: 23.1% in CD. IMM co-therapy was associated with increased TNFi persistence in CD (median 49.0 vs 25.0 months, HR = 0.67 95%CI:0.65-0.70, P0.001) and UC (32.0 vs 17.0, HR = 0.72 95%CI:0.68-0.76, P0.001). IMM co-therapy was not associated with vedolizumab persistence in CD (33.0 vs 36.0, HR = 0.95 95%CI:0.85-1.07, P=0.43), vedolizumab in UC (45.0 vs 48.0, HR = 0.93 95%CI:0.84-1.02, P=0.11) or ustekinumab in CD (median 52 months, HR = 0.91 95%CI:0.82-1.03, P=0.13). IMM co-therapy in bio-exposed UC patients was associated with increased vedolizumab persistence (median 37.0 vs 30.0, HR = 0.84 95%CI:0.72-0.97, P=0.02). IMM co-therapy in bio-exposed CD patients was not associated with vedolizumab (P=0.28) or ustekinumab (P=0.24) persistence. Patients with ≥3 months of IMM co-therapy at induction before IMM de-escalation had better persistence than those who stopped earlier for both CD (P0.001) and UC (P0.001). There was no difference between thiopurine and methotrexate co-therapy for CD (P=0.41) or UC (P=0.45). Conclusion IMM co-therapy improves TNFi persistence, but not vedolizumab or ustekinumab. At least three months of initial IMM co-therapy may enhance TNFi persistence. Methotrexate demonstrated no significant difference in benefit compared to thiopurines. Conflict of interest: Dr. Gu, Bonita: Dr Bonita Gu has received sponsorship for conference attendance from Johnson & Johnson and Ferring. Chetwood, John D: Speaker fees: Novartis, Eli Lilly, Dr Falk Pharma, Johnson & Johnson Pudipeddi, Aviv: Aviv Pudipeddi has received speaker honoraria or advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Johnson & Johnson, Pfizer and Takeda. Yau, Yunki: No conflict of interest Kariyawasam, Viraj: Educational grants or research support – Ferring, Janssen, AbbVie, Takeda, Shire, WSLHD Research and Education network, Crohn’s and Colitis USA Speaker fees – Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Chiesi, Celltrion, GSK, Eli-Lilly, Research Review, Limbic Advisory boards – Janssen, Takeda, Ferring, AbbVie Board director- IBD Sydney organisation (not for profit) Paramsothy, Sudarshan: SP has served as a consultant for Vedanta Biosciences and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert W: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer